Delving into the Latest Updates on Foscenvivint with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

+ [1]

Target

CTNNB1

Mechanism

CTNNB1 inhibitors(Catenin beta 1 inhibitors)

Therapeutic Areas

Digestive System Disorders

Active Indication

Liver Cirrhosis

Inactive Indication

Acidemia, IsovalericAcute Myeloid LeukemiaAdenocarcinoma of large intestine+ [11]

Originator Organization

PRISM BioLab Co., Ltd.

Active Organization

Tokyo Metropolitan Komagome Hospital

Inactive Organization

PRISM BioLab Co., Ltd.

Ohara Pharmaceutical Co., Ltd.PRISM Pharma Co., Ltd.

Drug Highest PhasePhase 2

First Approval Date-

Regulation-

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Structure

Molecular FormulaC33H35N6O7P

InChIKeyVHOZWHQPEJGPCC-AZXNYEMZSA-N

CAS Registry1422253-38-0

Proliferation and transdifferentiation of the retinal pigment epithelium (RPE) are hallmarks of proliferative vitreoretinopathy (PVR); however, the critical regulators of this process remain to be elucidated. Here, we investigated the role of tenascin-C in PVR development. In vitro, exposure of human ARPE-19 (hRPE) cells to TGF-β2 increased tenascin-C expression. Tenascin-C was shown to be involved in TGF-β2-induced transdifferentiation of hRPE cells, which was inhibited by pretreatment with tenascin-C siRNA. In PVR mouse models, a marked increase in the expression of tenascin-C mRNA and protein was observed. Additionally, immunofluorescence analysis demonstrated a dramatic increase in the colocalization of tenascin-C with RPE65 or α-smooth muscle actin(α-SMA) in the epiretinal membranes of patients with PVR. There was also abundant expression of integrin αV and β-catenin in the PVR membranes. ICG-001, a β-catenin inhibitor, efficiently attenuated PVR progression in a PVR animal model. These findings suggest that tenascin-C is secreted by transdifferentiated RPE cells and promotes the development of PVR via the integrin αV and β-catenin pathways. Therefore, tenascin-C could be a potential therapeutic target for the inhibition of epiretinal membrane development associated with PVR.

01 Sep 2024·Acta Pharmaceutica Sinica B

Transferrin receptor-targeted immunostimulant for photodynamic immunotherapy against metastatic tumors through β-catenin/CREB interruption

Article

Author: Yu, Baixue ; Zhang, Wei ; Li, Xiaotong ; Cen, Yi ; Yan, Mengyi ; Chen, Xiayun ; Liu, Qianqian ; Chen, Ying ; Li, Shiying ; Li, Xinxuan ; Wang, Tao ; Liu, Yibin

The immunosuppressive phenotype of tumor cells extensively attenuates the immune activation effects of traditional treatments. In this work, a transferrin receptor (TfR) targeted immunostimulant (PTI) is fabricated for photodynamic immunotherapy against metastatic tumors by interrupting β-catenin signal pathway. To synthesize PTI, the photosensitizer conjugated TfR targeting peptide moiety (Palmitic-K(PpIX)-HAIYPRH) is unitized to encapsulate the transcription interrupter of ICG-001. On the one hand, the recognition of PTI and TfR can promote drug delivery into tumor cells to destruct primary tumors through photodynamic therapy and initiate an immunogenic cell death with the release of tumor-associated antigens. On the other hand, PTI will interrupt the binding between β-catenin and cAMP response element-binding protein (CREB), regulating the gene transcription to downregulate programmed death ligand 1 (PD-L1) while upregulating C-C motif chemokine ligand 4 (CCL4). Furthermore, the elevated CCL4 can recruit the dendritic cells to present tumor-specific antigens and promote T cells activation and infiltration, and the downregulated PD-L1 can avoid the immune evasion of tumor cells and activate systemic anti-tumor immunity to eradicate lung metastasis. This work may inspire the development of antibody antibody-free strategy to activate systemic immune response in consideration of immunosuppressive conditions.

01 Sep 2024·The American Journal of Pathology

TGFβ1-Induced Fibrotic Responses of Conjunctival Fibroblasts through the Wnt/β-Catenin/CRYAB Signaling Pathway

Article

Author: Zhou, Biting ; Lin, Yijun ; Yao, Yihua ; Wang, Xiaohui ; Yang, Juhua ; Zhu, Yihua ; Chen, Kaiping

Conjunctival fibrosis is a common postoperative complication of glaucoma filtration surgery, resulting in uncontrolled intraocular pressure and surgery failure. Therefore, it is urgent to understand the molecular mechanisms underlying conjunctival fibrosis and to explore novel pharmacologic anti-fibrosis therapies for glaucoma filtration surgery. The 4D-DIA quantitative proteomic results, coupled with experimental data, revealed the activation of the Wnt/β-catenin pathway in transforming growth factor (TGF)-β1-induced human conjunctival fibroblasts (HConFs). Treatment with ICG-001, a Wnt/β-catenin inhibitor, effectively inhibited cell proliferation and migration in TGFβ1-treated HConFs. ICG-001 treatment alleviated the increased generation of extracellular matrix proteins induced by TGFβ1. In addition, ICG-001 reduced the expression level of α smooth muscle actin (α-SMA) and inhibited cell contractility in TGFβ1-treated HConFs. Proteomics data further suggested that αB-crystallin (CRYAB) was a downstream target of Wnt/β-catenin, which was up-regulated by TGFβ1 and down-regulated by ICG-001. Immunoblotting assay also indicated that ICG-001 reduced the expressions of ubiquitin and β-catenin in TGFβ1-treated HConFs, implying that CRYAB stabilized β-catenin by inhibiting its ubiquitination degradation. Exogenous CRYAB promoted cell viability, increased extracellular matrix protein levels, and up-regulated α-SMA expression of HConFs under TGFβ1 stimulation. CRYAB rescued TGFβ1-induced fibrotic responses that were suppressed by ICG-001. In conclusion, this study elucidates the regulatory mechanism of the Wnt/β-catenin/CRYAB pathway in conjunctival fibrosis, offering promising therapeutic targets for mitigating bleb scarring after glaucoma filtration surgery.

100 Deals associated with Foscenvivint

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External Link

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB15034

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Liver Cirrhosis	Phase 2	JP	Ohara Pharmaceutical Co., Ltd.	24 Jul 2018
Acidemia, Isovaleric	Phase 2	US	PRISM Pharma Co., Ltd.	01 Nov 2015
Adenocarcinoma of large intestine	Phase 2	US	PRISM Pharma Co., Ltd.	01 Nov 2015
Metastatic Colorectal Carcinoma	Phase 2	US	PRISM Pharma Co., Ltd.	01 Nov 2015
Acute Myeloid Leukemia	Phase 2	US	PRISM BioLab Co., Ltd.	-
Philadelphia chromosome positive chronic myelogenous leukemia	Phase 2	US	PRISM BioLab Co., Ltd.	-
Hepatitis C	Preclinical	JP	Ohara Pharmaceutical Co., Ltd.	24 Jul 2018
Liver Cirrhosis	Preclinical	JP	Ohara Pharmaceutical Co., Ltd.	24 Jul 2018
Acute Myeloid Leukemia	Preclinical	US	PRISM BioLab Co., Ltd.	-
Philadelphia chromosome positive chronic myelogenous leukemia	Preclinical	US	PRISM BioLab Co., Ltd.	-

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT04047160 (Pubmed) Manual	Phase 1	Primary Biliary Cholangitis	7	OP-724	(ndapyojbue) = djbfpgceoo hmvxhhzhdl (fzizqykarv ) View more	Positive	01 Nov 2022
NCT03620474 (Pubmed) Manual	Phase 1/2	Liver Cirrhosis	27	PRI-724 (phase 1)	-	Positive	20 May 2022
NCT03620474 (Pubmed) Manual	Phase 1/2	Liver Cirrhosis	27	PRI-724 (phase 2a)	(ubrihbqtoe) = psbnqollyq uvhlgdtcfs (yuiofebduo ) View more	Positive	20 May 2022
NCT01764477 (ASCO2016) Manual	Phase 1	Advanced Pancreatic Adenocarcinoma Second line	20	gemcitabine+PRI-724	(lonpeiwamb) = none mmhquoucay (exrzsowkom ) View more	Positive	03 Jun 2016
NCT01764477 (ASCO2015)	Phase 1	Advanced Pancreatic Adenocarcinoma Second line	10	PRI-724	(jprdyxasfq) = ylclqetmmu qfmgjbbesm (plgvebupfo )	-	20 May 2015
NCT01302405 (ASCO2013)	Phase 1	HR-positive/HER2-low Solid Tumors	18	PRI-724	(rruovapeia) = sjtwxtoucf yvnkdyubxi (ctkeigavia ) View more	-	20 May 2013